Project Summary/Abstract Substance use costs society $740 billion dollars each year, placing an enormous burden on our nation?s health care and criminal justice systems. Approximately 85% of incarcerated offenders in the United States have a history of substance use and/or are imprisoned for crimes involving or motivated by alcohol and/or drug use. Incarcerated individuals tend to show poorer outcomes following substance use treatment, and forced abstinence via imprisonment is associated with risk for future substance use, which likely contributes to substance-related antisocial behavior following imprisonment. Over the past few decades, women have been sentenced to prison for drug-related reasons at alarming rates, with a growth rate exceeding that for men. Further, women offenders tend to be impacted more heavily by substance use with co-morbid psychopathology, placing greater demands on the system in terms of substance use and mental health treatments. Using the world?s largest forensic neuroimaging database on women offenders (SWANC-F), this proposal investigates substance use and related antisocial behavior following release from prison in a large sample of women offenders, with a focus on neurobiological mechanisms, to demonstrate the utility of brain measures in estimating long-term substance use outcomes in at-risk women. Substance-related antisocial behavior, defined as committing crime(s) related to substance use after release from prison, will be obtained from re-arrest data in institutional files and comprehensive background checks on all women enrolled in the study. A random sample (n = 100) will then be followed-up with via phone to gather data on substance use and obtain supplemental information to corroborate re-arrest data from files and background checks. Employing regression analyses and machine learning/pattern classifier approaches, models will be compared testing effects of psychiatric and socioeconomic variables, along with resting-state functional connectivity (rsFC) brain measures, to examine unique and combined effects in differentiating among heterogeneous etiological mechanisms driving substance use outcomes of interest in women. Specifically, this proposal seeks to test the extent to which psychiatric and socioeconomic factors confer risk for substance-related antisocial behavior following release from prison in women (Aim 1), and integrates and compares the utility of rsFC brain measures in improving these prediction models (Aim 2). Then, similar methods will be applied to test the prediction of substance use following release from prison (Aim 3). It is expected that psychiatric risk factors and socioeconomic protective factors, as well as rsFC brain measures, will be useful in predicting substance use and related antisocial behavior following incarceration, along with time elapsed between release from prison and initiation of substance use and related behavior. Testing factors that aid in predicting these behaviors in women has the potential to be far-reaching by informing the development of targeted treatments, including those that help to account for sex differences and co-morbid conditions related to substance use.